Method of treating burned skin

ABSTRACT

A METHOD FOR THE TREATMENT OF THERMAL BURNS OF THE SKIN OF MAMMALS BY THE INDUCEMENT OF CALCIPHYLAXIS.

Patented Apr. 11, 1972 US. Cl. 424-444 4 Claims ABSTRACT OF THE DISCLOSURE A method for the treatment of thermal burns of the skin of mammals by the inducement of calciphylaxis.

CROSS REFERENCE To RELATED APPLICATIONS This application is a continuation-in-part of copending US. application Ser. No. 627,295, now abandoned.

SUMMARY OF THE INVENTION This invention relates to a method of treating thermal burns of the skin of mammals. In a particular aspect, it relates to a method of treating thermal burns of the skin of mammals by the inducement of Calciphylaxis.

Calciphylaxis is a hypersensitivity reaction resulting from the administration of, or endogenous production of, a sensitizing calcifier in combination with a challenger. Usually a critical period must elapse between sensitization and challenge, Sensitizing calcifiers include vitamin D compounds, dihydrotachysterol and parathyroid hormone, among others. The challenger may in itself be innocuous, such as plucking a few hairs, pinching the skin, or administering such substances as metallic salts or egg albumen. The reaction was first discovered by Hans Selye and is described by him in Calciphylaxis, University of Chicago Press, 1962. Calciphylaxis has been repeatedly induced in experimental animals, but heretofore no therapeutic method based on this physiological response has been developed.

It is an object of this invention to prdvide a method of treating thermal burns of the skin of mammals.

It is a second object of this invention to provide a method of treating thermal burns of the skin of mammals by inducing a localized calciphylactic reaction.

Other objects of this invention will be obvious to those skilled in the art from the disclosure herein.

The discovery of this invention is a method for treating thermal burns of the skin of mammals by the inducement of a calciphylactic reaction in the traumatized skin, i.e. a thermal burn ranging in severity from mild injury to extensive necrosis of the skin and/ or underlying tissues. Generally, the method is most suitable for third degree burns, because first and second degree burns generally heal satisfactorily without scarring. Animals having third degree burns over 75% of their bodies have recovered fully following the treatment of this invention without development of scar tissue. It is contemplated that the method is suitable, not only for accidental burns, but also intentional ones. The latter category, especially in humans, includes the embodiment of the use of thermal burns for the destruction of birthmarks, disfiguring scars resulting from earlier injury, and the like. Accordingly, the term skin is intended to include such abnormalities as birthmarks and scars. The method is widely applicable provided calciphylaxis is induced before the development of shock or other stress reaction.

DETAILED DESCRIPTION According to the method of this invention, the sensitizing calcifier is administered within about 24 hours of the burn. If the burn is to be applied intentionally as for cosmetic purposes, the sensitizing calcifier preferably is administered prior to the burn. If the burn is accidental, the sensitizing calcifier as defined hereinafter, is administered, according to the preferred embodiment of this invention, within 24 hours following the burn and before shock or stress reaction occurs.

It is contemplated that the invention is broadly applicable to mammals in general. In particular the method is applicable to mammal species known to exhibit the phenomenon of calciphylaxis. As reported by Selye in the foregoing reference at p. 292 and following, calciphylaxis has been experimentally induced in the cat, dog, golden hamster, monkey, rat, mouse, guinea pig, and the rabbit.

In the preferred embodiment of this invention dihydrotachysterol (DHT) is employed as the sensitizing calcifier and is administered orally at a dose of about 3 ml. at about 0.05 mg./ml. (about 5 mg./kg.) within about 24 hours of the occurrence of the trauma. The burn constitutes the challenger. Calciphylaxis of the burned tissue begins promptly and calcification is complete within a few days. During the several succeeding weeks, usually about three weeks, new skin gradually grows under the calcified tissue (i.e. the plaque). When the area has healed, the plaque drops off spontaneously and the animal is healed.

In another embodiment of this invention, a challenger, as defined hereinafter, is administered to the traumatized tissue, either 'by topical application or by subcutaneously infiltrating the tissues with a suitable solution. This embodiment is particularly useful when a period of more than 24 hours has elapsed following the injury, although it can be employed earlier. In this embodiment, the sensitizing calcifier is administered as before but in a higher dosage, i.e. about -85 ing/kg; then, about 24 hours following the trauma, the challenger is administered to the traumatized tissue, and calcification of the traumatized tissue begins.

In yet another embodiment, a direct calcifier i's administered, usually topically, to the traumatized tissue. A direct calcifier is a challenger to which the body is constantly sensitive. Such compounds apparently attract calcium to the traumatized tissues. Direct calcifiers include potassium permanganate, lead chloride (PbCl cesium chloride (CeCl and the like, several of which are khown.

Any sensitizing calcifier, several of which are known, can be used in the method of this invention. Among the known sensitizing calcifiers are dihydrotachysterol (DHT), vitamins D and D and sodium acetylsulfathiazole. DHT is preferred for the practice of this invention because it is a synthetic sterol which is commercially available in a high degree of purity. Generally, the amount of sensitizer can be varied widely. Conveniently, it can be dispersed in a suitable carrier, e.g. corn oil, at a concentration of about 0.0l1.0 mg./ml. and administered orally at a dosage of about 3-10 mg./kg. body weight, preferably about 5 mg./kg., according to the preferred embodiment, or about 80-85 mg./kg. when a challenger is to be applied.

Any suitable challenger, many of which are known, can be used in the practice of this invention. Among the known challengers are salts of iron, egg white and egg yolk. Ferric dextran is a preferred challenger and is commercially available in pure form. The amount of challenger employed can generally be varied within wide limits. Conveniently, the injured area is freely treated with solutions or ointments of the challenger.

EXAMPLE 1 A solution of DHT in corn oil, 0.05 mg./ml., was administered orally at a rate of 3 ml. per animal to each of 5 female mice, age 3 months, mean weight 30 g. After 24 hours, the animals were anesthetized with ether and a circular burn, approximately cm. in diameter (about 20 cm. was given each animal on a shaved dorsal section of skin. The burn was given by applying to the skin a soldering iron having a round, flat tip instead of the customary pointed tip. The temperature of the soldering iron was about 1000 F. and was left in contact with the skin for a period of about 5 seconds, sufficient to produce a third degree burn.

The animals were returned to their cages and treated every day for the remainder of the recuperative period by exposure to ultra-violet light to reduce the incidence of infection.

Two days after the burn, a calcium plaque was observed forming in the traumatized, necrotic tissue. The calcification reaction continued for 5 days, forming a hard plaque.

On the 21st day following the burn, fissures began to appear in the plaque, and on the 24th day the plaque dropped ofi revealing new skin and hair, free from scars and blemishes and free from adhesion to underlying tissues.

At no time did the animals display evidence of pain or discomfort.

EXAMPLE 2 Ten female mice, age 3 months, mean weight 30 g., were anesthetized and a deep circular burn was inflicted on a shaved dorsal section of the animal as in Example 1. The burned area was promptyly covered with 5 ml. of pharmaceutical grade cellulose gel containing 0.5 g. of potassium permanganate (equivalent to 25 mg./cm. of burned skin) dispersed therein. A gauze bandage was placed over the gel and burned area to prevent dislodgment. The animals were removed to their cages where they were observed daily. Upon awakening, the animals displayed no evidence of pain or discomfort except thrist.

On the 3rd day the calcium plaque was observed forming, and by the 5th day the plaque was well-defined. By the 24th day new skin was observed invading the plaque, and about a week later the healing process was complete.

This example demonstrates the unique action of potassium permanganate as a direct calcifier, i.e. it causes calcium deposition without previous sensitization.

EXAMPLE 3 Burns were inflicted on 5 female mice, age 3 months, mean weight 30 g., by the technique of Example 1. Two days later, the animals were sensitized by oral administration of 5 ml. of a corn oil solution of DHT (0.5 mg./ ml. of corn oil). About 24 hours later, 3 ml. of aqueous ferric dextran solution (the challenger), having an iron concentration of 20 mg./ml., (about 3 mg. of iron/cm? of burned skin) was infiltrated subcutaneously around v the damaged area, which was then covered with a sterile gauze. The animals were than returned to their cages for observation.

The animals showed no evidence of pain or discomfort following application of the ferric dextran, although -some edema developed after administration of the ferric dextran. On the 5th day after sensitization the calcium plaque begin to form, and by the 7th day it was complete. By the 18th day fissures began to appear in the plaque, and on the 23rd day the plaque was shed, revealing fine new skin, free from the scars and blemishes which were present before infliction of the burn.

We claim:

1. A method for treating a thermal burn of the skin of a mammal consisting of the step of inducing calciphylaxis in said burned skin by orally administering to said mammal at a dose of about 3-10 mg./ kg. a sensitizing calcifier selected from the group consisting of dihydrotachysterol, vitamin D vitamin D and sodium acetylsulfathiazole within 24 hours of the occurrence of said burn.

2. The method of claim 1 consisting of administering orally to said mammal, dihydrotachysterol at a dosage of about 3-10 mg./kg., as said sensitizing calcifier, within 24 hours after the occurrence of said skin burn, thereby inducing calciphylaxis in said burned skin.

3. A method for treating a thermal burn of the skin of a mammal consisting of administering a sensitizing calcifier selected from the group consisting of dihydrotachysterol, vitamin D vitamin D and sodium acetylsulfathiazole orally at a dosage of from -85 mg./kg. thereby inducing calciphylaxis in said burned skin, then, within about 24 hours, administering to said burned skin by topical application, or by subcutaneous infiltration of the burned tissues, a solution of ferric dextran as a challenger at a dosage of about 3 mg. iron/cm. of said burned skin.

4. A method for treating a thermal burn of the skin of a mammal consisting of administering a solution of potassium permanganate topically to said burned skin as a direct calcifier at a dosage of about 25 mg. of potassium permanganate, per square centimeter of burned skin thereby inducing calciphylaxis in said burned skin.

References Cited Selye Ca1ciphylaxis (1962), University of Chicago Press, pp. 37, 47, 57, 63, 291, 292, 311, 433, 434, 460 and 461.

SAM ROSEN, Primary Examiner US. or. X.R. 

